Ketonemia and Ketogenesis Regulation lec3

Ketonemia

• Ketonemia is the presence of excess ketone bodies in the blood.
• It is usually caused by increased production of ketone bodies by the liver rather than reduced utilization by extrahepatic tissues.

Ketone Bodies

• Acetoacetate and 3-hydroxybutyrate can be readily reformed into acetyl-CoA.
• Acetone is difficult to reform into acetyl-CoA and is largely volatilized in the lungs.

Regulation of Ketogenesis

• Ketogenesis is mainly regulated by nutritional status.
• After uptake of free fatty acids by the liver, they can be:
  • β-oxidized to form acetyl-CoA that enters the citric acid cycle, with excess acetyl-CoA forming ketone bodies.
  • Esterified to form triacylglycerol and phospholipid.

Carnitine Palmitoyltransferase-I (CPT-I)

• CPT-I regulates the entry of fatty acids into the oxidative pathway.
• CPT-I activity is affected by nutritional status:
  • In a well-carbohydrate-fed state:
    • CPT-I activity is low.
    • Lipolysis is decreased.
    • β-oxidation and ketogenesis are depressed.
    • Most fatty acids are esterified to form triacylglycerol and phospholipid.
  • In starvation or a low-carbohydrate diet:
    • CPT-I activity is high.
    • Lipolysis is increased.
    • β-oxidation is increased.
    • More acetyl-CoA is converted to ketone bodies.

Clinical Aspects of Ketogenesis

• Ketoacidosis results from prolonged ketosis.
• Higher-than-normal quantities of ketone bodies in the blood and/or urine constitute ketonemia (hyperketonemia) and/or ketonuria, respectively.
• Ketosis occurs in:
  • Starvation.
  • Pathologic states, such as:
    • Diabetes mellitus due to:
      • Reduced glucose utilization for energy production.
      • Excess lipolysis due to the absence or defect of insulin.
    • Hypoglycemia due to:
      • Reduced glucose concentration available for energy production.
      • Excess lipolysis due to the reduction of insulin.